In three patients whose Guillain-Barré syndrome (GBS) was preceded by gastrointestinal infection due to Campylobacter jejuni, gammadelta T cells were generated from peripheral blood in response to in vitro stimulation with C. jejuni. In one of the patients, where a diagnostic sural nerve biopsy was performed, gammadelta T cells were also isolated following culture of the nerve tissue. Studies with healthy volunteers and C. jejuni gastroenteritis patients also showed preferential enrichment for gammadelta T cells in peripheral blood cells stimulated with C. jejuni, although the response was significantly lower than that seen in GBS patients. In two out of three GBS patients and all of the controls, gammadelta T cell receptor (TCR) gene usage was shown to be Vgamma9/Vdelta2+. In the GBS patient where nerve-infiltrating gammadelta T cells were isolated, these and C. jejuni-specific peripheral blood cells had similar TCR gene usage, predominantly consisting of Vgamma5/Vdelta1+ cells. Sequencing the Vdelta1 products from nerve and peripheral blood showed similarities in CDR3 length, but the single Vdelta1 sequence obtained from nerve was not identified in peripheral blood. These results suggest that the generation of gammadelta T cells is part of a normal immune response to C. jejuni, which, in patients with GBS, may contribute to the pathogenesis of their inflammatory neuropathy.